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Biomedical subjects

Y Furuhashi

Publications and source records attributed to Y Furuhashi.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mitomycin C cross-resistance induced by adriamycin in human ovarian cancer cells in vitro.

We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a greater than 5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Alpha-fetoprotein in malignant germ cell tumors of the ovary.

To investigate the clinical significance of alpha-Fetoprotein (AFP) in malignant germ cell tumors of the ovary, we studied 46 patients who were treated by the Tokai Ovarian Tumor Study Group. The 46 patients had the following tumors: immature teratoma (IT), 17 cases; endodermal sinus tumor (EST), 16 cases; mixed germ cell tumor containing EST, 11 cases; embryonal carcinoma, 1 case; polyembryoma, 1 case. In all 29 non-IT cases, AFP was positive, and in 27 cases (93%) the level was above 1000 ng/ml. In 11 of 17 cases of IT (64.7%), AFP levels were elevated and in 1 case the level was above 1000 ng/ml. Elevation of the AFP level above 1000 ng/ml suggested the presence of EST. AFP levels were monitored in 27 of 29 cases without IT during treatment and follow-up. It was found that AFP levels should be monitored closely for at least 1 year after induction of remission. No recurrence was observed when AFP continued to be negative longer than 1 year. The mean interval to clinical recurrence from the reelevation of AFP was 4 months (1.4-9 months). An increase in the AFP to a positive level, even without clinical signs of recurrence, should be regarded as a recurrence. AFP was found to be a useful tumor marker for the diagnosis and management of malignant germ cell tumors of the ovary.

Adult↗
PubMed1990

Establishment of hybridomas secreting monoclonal antibodies to placental alkaline phosphatase and development of an enzyme immunoassay for its determination.

We established seven hybridomas secreting murine IgG monoclonal antibodies (MoAbs) to placental alkaline phosphatase (PLAP). The seven hybridomas were designated (1) 7C6, (2) 6G10, (3) 5B9, (4) 6D5, (5) 6B5, (6) 11G6 and (7) 3E10, respectively. The characteristics of these hybridomas were evaluated by radioimmunoassay (RIA) with 125I-PLAP. Their reactivity with the intestinal alkaline phosphatase, one of the alkaline phosphatase isozymes, was (1) 0.04, (2) 0.2, (3) 1.4, (4) 1.8, (5) 0, (6) 4.0 and (7) 6.2(%), respectively. None of them showed signs of cross-reactivity with the liver-type alkaline phosphatase, also one of the alkaline phosphatase isozymes, within a PLAP concentration of 2,000 IU/l. The subtype of 5B9 was IgG1, and that of the others was IgG2a. We then used 7C6, to develop a sensitive, specific and convenient enzyme immunoassay (EIA) for the determination of PLAP, and assayed sera from patients with various gynecologic diseases. The incidence of increased PLAP was 6.4% in patients with benign diseases, 21.5% in cervical cancer, 36.4% in endometrial carcinoma, and 39.5% in malignant ovarian tumors. The specificity for malignant diseases seemed to be higher than that of CA125. Among endometrial carcinomas, well-differentiated adenocarcinoma had the highest incidence of an increased concentration. Among malignant ovarian tumors, serous cystadenocarcinoma, endometrioid carcinoma, dysgerminoma and Krukenberg's tumor showed a higher incidence than the other types.

Alkaline Phosphatase↗
PubMed1990

Simultaneous measurement of CA 125, CA 19-9, tissue polypeptide antigen, and immunosuppressive acidic protein to predict recurrence of ovarian cancer.

We studied the utility and limitations of CA 125 for the early diagnosis of recurrence of ovarian cancer and investigated whether the precision of diagnosis could be enhanced by combining CA 125 with other tumor markers. Of 181 patients with epithelial ovarian cancer, 149 were in clinical remission and 35 had developed recurrence. Thirty-four women with recurrence had preoperative CA 125 values of 35 U/mL or more, and 21 (62%) had CA 125 levels of 35 U/mL or more at the time of detection of clinical recurrence. Eleven had levels that remained elevated 3 months before identification of the recurrence. However, in 13 cases CA 125 was below 35 U/mL at the time recurrence was detected. To enhance the efficacy of tumor markers to predict recurrence, patients in whom multiple tumor markers had been measured were studied retrospectively. At the time of clinical recurrence and 3 months earlier, the diagnostic sensitivity of CA 125 alone for recurrence was 64 and 33%, respectively, whereas the sensitivity of a combination of tumor markers (CA 125, CA 19-9, tissue polypeptide antigen, and immunosuppressive acidic protein) was 89 and 66%. Thus, prediction of recurrence of ovarian cancer can be improved by the use of a combination of these tumor markers.

Adenocarcinoma↗
PubMed1989

Three-year prospect of patients with common epithelial carcinoma of the ovary.

In order to forecast the survival of patients, we collected 417 cases of common epithelial carcinoma of the ovary as a population for this study, then selected 141 cases who had survived more than 3 years and 131 cases who had died within 3 years as a sample of statistical inference. The sample was computerized inputting 25 factors which were obtained mainly on the first surgery. We selected 8 factors with 46 items considering their weight to forecast the prognosis on convenience. The selection of factors was carried out by following three basic principles. First, we selected factors that retained high partial correlation coefficients. Second, we selected factors which did not overlap each other in their contents. Third, we selected factors which were not decided intentionally. Accordingly, the score for forecasting the 3-year survival of patients with ovarian carcinoma was framed. The correct discrimination rate of the score when it was judged at the 0 point was 86.8% in the sample group. However, in the sample group outside the population, it was 83.1%.

Adult↗
PubMed1989

Specific inhibitory substance to the husband's HLA allotype in sera from patients with gestational trophoblastic disease detected by lymphocytotoxicity testing.

The sera of nine patients with gestational trophoblastic disease were investigated for the inhibitory substance specific to the HLA allotypes of the patients' husbands by microcytotoxicity inhibition testing using monoclonal antibodies (anti-A2, A9, A10) and HLA-typing serum to Bw52. The specific inhibitory substance was present in three of three choriocarcinoma patients, in three of four invasive mole patients, and in one of two hydatidiform mole patients and seemed to change in titer parallel with tumor growth. These facts suggest that the inhibitory substance could have some relation to the patient's immunological response against the tumor; that is, this inhibitory substance could be the reason why patients could not induce graft rejection response to trophoblastic tumor cells.

Antibodies, Monoclonal↗
PubMed1988

Methotrexate-induced resistance to dactinomycin in choriocarcinoma.

NaUCC-2, a choriocarcinoma cell line, was derived from a patient who had a very poor clinical response to combination chemotherapy. Methotrexate (MTX) might have inhibited the antitumor effect of dactinomycin. To investigate this point, in vitro studies were performed to determine the sensitivity and uptake of MTX and dactinomycin (administered individually and in combination) to NaUCC-2 and three other choriocarcinoma cell lines. Dihydrofolate reductase (DHFR) concentrations were studied as well. Although NaUCC-2 showed sensitivity to MTX and dactinomycin, which were comparable to the other cell lines when they were given separately, NaUCC-2 was unique in that the combination of MTX and dactinomycin was less lethal than dactinomycin given by itself. The uptake of MTX in NaUCC-2 was significantly higher than that in the other cell lines, and MTX also induced an increase in dactinomycin uptake in NaUCC-2. There was no significant difference in DHFR activity. Although additional studies are necessary to determine the mechanism responsible for this effect, these findings suggest that a mechanism other than drug uptake or DHFR activity must play a role in the drug resistance for choriocarcinoma. These findings also suggest that the most commonly used combination chemotherapy for choriocarcinoma, dactinomycin and MTX, may not always be the best method.

Adult↗
PubMed1988

[Recent advances in the treatment of choriocarcinoma].

Recent advances in intensive care procedures have improved the therapeutic results of choriocarcinoma treatment. The mortality of patients with choriocarcinoma, which was 100% in 1958, has gradually decreased, and finally fell to about 10% in 1983. These favorable results have been mainly due to the progress made in chemotherapy, including combined administration of methotrexate and actinomycin-D. However, recent progress has been chiefly dependent on intensive care procedures, involving so-called multidisciplinary treatment, including surgical treatment for pulmonary or intracranial metastatic foci and whole-brain irradiation. When the treatment results for choriocarcinoma were compared between metastatic and non-metastatic cases, the mortality, which had decreased for both groups with time, had already reached 0% in non-metastatic cases, although it was still about 20% in metastatic cases. These results have made it clear that the most important aspect is how to treat choriocarcinoma metastatic foci. With the goal of finding some form of treatment that will help to attain complete cure of choriocarcinoma, we present here details of recent progress made in choriocarcinoma treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Dissociation of hCG-receptor complex and detection of hCG receptors in human chorionic tissues.

We developed a radioreceptor assay (RRA) system for investigating occupied hCG receptors by using a rat testis membrane fraction. Treatment with dithiothreitol, neuraminidase, and low pH (3.3) buffer partially dissociated hCG from its receptor with dissociation rates of 42.8%, 35.2%, and 68.7%, respectively. Specific receptor rebinding was unaffected and showed competitive inhibition of [125I]hCG rebinding by unlabeled hCG. Scatchard plot analysis yielded a rebinding Km of 1.798-3.496/pM. High concentrations of NaCl and MgCl2 had no obvious effect on the [125I]hCG-receptor complex. Triton X-100 and high concentration MnCl2 treatments resulted in the loss of the receptor rebinding activity. We also investigated human chorionic tissue (at 8 weeks, 11 weeks, 16 weeks, 24 weeks, and term) for hCG receptors using the above method. Treatments with different agents increased [125I]hCG binding in this tissue preparation 139-226%, but Scatchard analysis failed to demonstrate any specificity. [125I]hCG uptake by the choriocarcinoma BeWo cell-line increased 151-193% after similar treatments, but this increase could not be competitively inhibited by unlabeled hCG. Treatment with dithiothreitol, neuraminidase, and low pH (3.3) buffer seems feasible for detecting hCG-occupied receptors. Our results suggest that there are no hCG receptors distributed on the surface of the syncytiotrophoblast of human placenta.

Adult↗
PubMed1987

Growth stimulation of human melanocytes: identification and characterization of melanoma-derived melanocyte growth factor (M-McGF).

The melanocyte growth stimulating factor from human melanoma cells grown in vitro [Eisinger, M. et al, (1985) Science 229, 984-986] has been purified and identified as a 14 kDa peptide. The activity was shown to be sensitive to acid and heat treatments but resistant to reduction. The factor has strong affinity for heparin-Sepharose and was separated into two fractions by ion-exchange chromatography. Based on its properties, it is grouped in the family of heparin-binding growth factors. Identification of this growth factor will provide a tool for studies of growth regulation of normal and transformed human melanocytes.

Cell Division↗
PubMed1987

Radioimmunoassay of the serum free beta-subunit of human chorionic gonadotropin in trophoblastic disease.

We developed a RIA specific for the free beta hCG employing anti-beta hCG monoclonal antibody 1D12. This RIA was highly sensitive to free beta hCG; the minimum detectable concentration was 0.4 ng/ml. alpha hCG, LH, beta LH, and FSH had little effect in the assay; the cross-reactivity of hCG was about 4%. Using this RIA, we measured serum free beta hCG concentrations in 38 normal pregnant women and 72 untreated patients with 3 types of trophoblastic disease: hydatidiform mole (n = 15), invasive mole (n = 29), and choriocarcinoma (n = 28). All of these samples were simultaneously assayed for hCG by RIA. In normal pregnant women, serum hCG changed as pregnancy progressed, but serum free beta hCG was not detected at any time. In contrast, serum free beta hCG was measurable in the majority of patients with trophoblastic disease. Strong correlations were found between the concentration of free beta hCG and that of hCG in each type of trophoblastic diseases. The mean free beta hCG to hCG ratio was lowest for hydatidiform mole and highest for choriocarcinoma, and the difference between the ratios in these 2 groups was statistically significant. Serial measurements in 7 patients with trophoblastic disease failed to reveal remarkable changes in the free beta hCG to hCG ratio throughout their clinical course. We conclude that the production of free beta hCG increases with the immaturity of the trophoblastic cell, and the degree of differentiation of trophoblastic cells may be reflected by the free beta hCG to hCG ratio.

Adult↗
PubMed1987

[Significance of tumor markers in the treatment of patients with ovarian malignancies].

Seven tumor markers (CA125, CA19-9, TPA, IAP, CEA, ferritin, LDH) were measured in 24 patients with ovarian cancer. The positive rates in untreated cases of ovarian cancer were 87.5% for CA125, 35.5% for CA19-9, 10% for CEA, 77.8% for IAP, 63.6% for TPA, 28.6% for LDH and 35.3% for ferritin. Among these, CA125 was the most available marker for detecting tumor growth or regression during each respective clinical course by serial measurement. Serial changes in serum alpha-fetoprotein (AFP) levels during treatment were studied among 27 patients with ovarian embryonal carcinoma. AFP decreased with a half-life of about 7 days, and was restored to the normal range within 10 weeks after the initial surgery and chemotherapy (VAC) in all cases. In subsequently fatal cases, AFP rose again during 10 to 30 weeks after the initial treatment.

Antigens, Neoplasm↗
PubMed1986

A new radioimmunoassay for human chorionic gonadotropin using monoclonal antibody.

A new radioimmunoassay (RIA) for human Chorionic Gonadotropin (hCG) was developed using murine monoclonal antibody to the beta-subunit of hCG (beta-hCG). The IgG fraction of the monoclonal antibody which did not react with 125I-beta-hCG was purified from hybridoma ascites, and covalently coupled to Sepharose 4B. This solid-phase antibody was incubated with standard hCG or serum sampled for 48 hours. The reaction medium was then removed by centrifugation and 125I-beta-hCG and anti-beta-hCG rabbit polyclonal antibody were added to the precipitate. The alcohol precipitation method was used for separating "bound" and "free" forms in the second reaction. The sensitivity for hCG in this assay system was 0.5 mIU/ml serum and the cross-reactivity with human Luteinizing Hormone (hLH) was 0.4%. This assay system was shown to be clinically applicable. Serial serum samples from two patients with trophoblastic disease were assayed and minute amounts of hCG, which could not be determined by conventional assay methods, could be assayed by this new RIA.

Adult↗
PubMed1986

Radioimmunoassay of placental alkaline phosphatase in ovarian cancer sera and tissues.

A specific radioimmunoassay for human placental alkaline phosphatase has been developed using the 125I-labeled enzyme, highly purified with a fast protein liquid chromatography system and an absorbed rabbit antiserum. The sensitivity of this assay was 0.2 U/L. Serum levels of over 0.2 U/L were found in 27% of ovarian cancer patients, and most of these elevated enzyme levels occurred with more advanced stages of the disease. On the other hand, almost all ovarian cancer tissue contained detectable levels of the enzyme. Serous adenocarcinoma, endometrioid adenocarcinoma, and dysgerminoma had particularly large amounts. Placental alkaline phosphatase was more frequently detected in tissue than in the serum of ovarian cancer, and therefore may be a useful target in immunodetection and immunotherapy and in studying the histopathology of ovarian cancer.

Adenocarcinoma↗
PubMed1986

Radioimmunodetection of human choriocarcinoma xenografts by monoclonal antibody to placental alkaline phosphatase.

Placental alkaline phosphatase (PLAP)-specific monoclonal antibody (MAb) 11-D-10, which did not react with other isoenzymes of alkaline phosphatase (AP), was raised by a hybridoma technique. MAb 11-D-10 was radiolabeled and administered to athymic mice bearing human choriocarcinoma containing PLAP. This antibody was found to be more specifically localized in tumor tissue as compared to normal tissues. The tissue-to-blood ratio (T/B ratio) of MAb 11-D-10 in tumor tissue increased from 1.38 at 2 days to 2.51 at 5 days after administration. On the other hand, the T/B ratios of isotype control non-immunized IgM in tumor tissue were 0.72 and 0.87 at 2 days and 5 days after administration, respectively. 131I-labeled MAb 11-D-10 was administered to athymic mice bearing choriocarcinomas of various sizes and various PLAP contents to examine the effect on the radioimage of the differences in tumor size and PLAP content. Tumors less than 0.3 cm in diameter could be imaged clearly by gamma-scintigraphy without blood pool image subtraction. The strength of the radioimage correlated fairly well with PLAP content.

Alkaline Phosphatase↗
PubMed1986

Purification of placental alkaline phosphatase and its monoclonal antibody.

Monoclonal antibodies (MAbs) to placental alkaline phosphatase (PAlP) were raised by using the hybridoma technique. Spleen cells from immunized mice were fused with the mouse myeloma line NS-1 using 50% polyethylene glycol and cultured in a selection medium. Antibodies were screened by the enzyme immunoassay using immobilized solid-phase antigen and anti-mouse immunogloblin Fab' (rabbit)-beta-D-galactosidase complex. Four double-cloned hybridomas were obtained. The cross-reactivity with different kinds of alkaline phosphatases of the raised MAbs was examined. At first, MAb 11-D-10, with which placenta was stained but liver and small intestine were not stained in indirect immunofluorescence, was selected. Then, the cross-reactivity of MAb 11-D-10 was further investigated by immunoblotting (Western blotting). MAb 11-D-10 reacted with PAlP but did not react with hepatic and intestinal alkaline phosphatase at all. The binding activity of 125I-labeled MAb 11-D-10 with different choriocarcinoma cell lines (SCH, BeWo, NaUCC-1, NaUCC-2, and NaUCC-3) was highest in SCH, then in the order of BeWo, NaUCC-3, NaUCC-1 and NaUCC-2, and correlated to the PAlP content of the cells (SCH greater than BeWo greater than NaUCC-3 greater than NaUCC-1 greater than NaUCC-2). Also the intensity of indirect immunofluorescence of the above cell lines with MAb 11-D-10 correlated with the PAlP content of each cell.

Alkaline Phosphatase↗
PubMed1985

Radioimmunolocalization of monoclonal antibodies to human chorionic gonadotropin in choriocarcinoma transplanted into athymic mice.

Radioimmunodetection of monoclonal antibodies to human Chorionic Gonadotropin (hCG) or its beta-subunit in choriocarcinoma tissue was investigated in athymic mouse model system. Antibody to hCG exhibited a higher localization index (L.I.) in tumor tissue than those in other organs, but the tissue/blood ratio of this antibody in tumor tissue was not so high as expected (0.38 and 0.5 on Day 2 and 5 respectively). On the other hand, antibody to beta-subunit showed the same L.I. in tumor tissue as those in other organs. Gel filtration of serum of mouse given an antibody to hCG showed that the antibody was forming immune complexes in the blood stream. Autoradiography showed many grains in the capillary vessels and intercellular spaces in the tumor tissue. We concluded that a monoclonal antibody to hCG localized in choriocarcinoma tissue via a mechanism of retention of immune complexes in the tissue, and that there may be a limitation to the clinical application of localization of antibodies to secretory products such as hCG of tumor cells from their low specific localization.

Animals↗